Emerging therapies for opioid-induced constipation: what can we expect?

INTRODUCTION: The rise in opioid use for managing chronic and oncologic pain has led to a significant increase in opioid-induced constipation (OIC) that impacts patient quality of life and pain management. AREAS COVERED: In this study, emerging therapies for OIC were criticized for refining advancements and novel treatment options. Key topics included the efficacy of peripherally acting mu-opioid receptor antagonists (PAMORAs) such as methylnaltrexone, naloxegol, and naldemedine, which specifically target opioid-induced gut dysfunction. Other treatment options, including intestinal secretagogues like lubiprostone and linaclotide, selective 5-HT receptor agonists such as prucalopride, and emerging adjunctive therapies like transcutaneous electrical nerve stimulation (TENS) and electroacupuncture were mentioned. Current guidelines from the American Gastroenterological Association (AGA) and the European consensus were criticized. EXPERT OPINION: Experts stress the importance of a stepwise approach to managing OIC, considering patient-specific factors and the efficacy of various treatments. While PAMORAs have demonstrated effectiveness in improving bowel function, their high cost and lack of extensive head-to-head comparisons with traditional laxatives are significant concerns. Emerging therapies and adjunctive treatments offer promising results but require further validation through rigorous studies. Future research should focus on long-term outcomes, cost-effectiveness, and comparative effectiveness to better address the complex needs of patients with OIC and refine treatment protocols.

Clinical implementation and evaluation of deep learning-assisted automatic radiotherapy treatment planning for lung cancer.

PURPOSE: The purpose of the study is to investigate the clinical application of deep learning (DL)-assisted automatic radiotherapy planning for lung cancer. METHODS: A DL model was developed for predicting patient-specific doses, trained and validated on a dataset of 235 patients with diverse target volumes and prescriptions. The model was integrated into clinical workflow with DL-predicted objective functions. The automatic plans were retrospectively designed for additional 50 treated manual volumetric modulated arc therapy (VMAT) plans. A comparison was made between automatic and manual plans in terms of dosimetric indexes, monitor units (MUs) and planning time. Plan quality metric (PQM) encompassing these indexes was evaluated, with higher PQM values indicating superior plan quality. Qualitative evaluations of two plans were conducted by four reviewers. RESULTS: The PQM score was 40.7 ± 13.1 for manual plans and 40.8 ± 13.5 for automatic plans (P = 0.75). Compared to manual plans, the targets coverage and homogeneity of automatic plans demonstrated no significant difference. Manual plans exhibited better sparing for lung in V5 (difference: 1.8 ± 4.2 %, P = 0.02), whereas automatic plans showed enhanced sparing for heart in V30 (difference: 1.4 ± 4.7 %, P = 0.02) and for spinal cord in Dmax (difference: 0.7 ± 4.7 Gy, P = 0.04). The planning time and MUs of automatic plans were significantly reduced by 70.5 ± 20.0 min and 97.4 ± 82.1. Automatic plans were deemed acceptable in 88 % of the reviews (176/200). CONCLUSIONS: The DL-assisted approach for lung cancer notably decreased planning time and MUs, while demonstrating comparable or superior quality relative to manual plans. It has the potential to provide benefit to lung cancer patients.

Designing sustainable mobile weight management applications: information technology (IT) experts perspectives.

Background: Weight management mobile applications have become increasingly popular as a tool for individuals to achieve their weight loss goals. However, key challenges with mobile weight management applications are sustaining user engagement and promoting long-term behavior change. This study examines the key functions and features of weight management mobile applications from the viewpoint of information technology (IT) experts. We have developed a framework that outlines the optimal design strategies for mobile apps to support sustainable weight management. Methods: We conducted face-to-face interviews with five experts to evaluate and give input on the proposed framework. Results: Eight specialized functionalities have been categorized and defined based on initial framework system features and recommended features based on experts' feedback: (I) customization; (II) usability; (III) integration; (IV) online support; (V) tracking; (VI) nutrition database; (VII) gamification; and (VIII) notification. In addition, common functionalities were identified as (I) registration/sign in; (II) data privacy; (III) security; and (IV) user feedback. An online discussion indicates the system functionality in four themes: (I) configuration; (II) data analytics; (III) support/performance; and (IV) platform: iOS, Android, Native. Conclusions: These functionalities and features will be incorporated into a framework to design mobile applications for sustainable weight management. Also, to be part of user interface development for the user experience experiments.

Exploring treatment decision-making in chronic myeloid leukemia in chronic phase.

The introduction of tyrosine kinase inhibitors (TKIs) has transformed the treatment of chronic myeloid leukemia (CML). Each approved TKI has its own risk-benefit profile, and patients have choices across lines of therapy. Identifying the initial and subsequent treatment that will lead to the best possible outcome for individual patients is challenging. In this review, we summarize data for each approved TKI across lines of therapy in patients with CML in chronic phase, highlighting elements of each agent's safety and efficacy profile that may impact patient selection, and provide insights into individualized treatment sequencing decision-making aimed at optimizing patient outcomes.

Towards AI-Driven Healthcare: Systematic Optimization, Linguistic Analysis, and Clinicians' Evaluation of Large Language Models for Smoking Cessation Interventions.

Creating intervention messages for smoking cessation is a labor-intensive process. Advances in Large Language Models (LLMs) offer a promising alternative for automated message generation. Two critical questions remain: 1) How to optimize LLMs to mimic human expert writing, and 2) Do LLM-generated messages meet clinical standards? We systematically examined the message generation and evaluation processes through three studies investigating prompt engineering (Study 1), decoding optimization (Study 2), and expert review (Study 3). We employed computational linguistic analysis in LLM assessment and established a comprehensive evaluation framework, incorporating automated metrics, linguistic attributes, and expert evaluations. Certified tobacco treatment specialists assessed the quality, accuracy, credibility, and persuasiveness of LLM-generated messages, using expert-written messages as the benchmark. Results indicate that larger LLMs, including ChatGPT, OPT-13B, and OPT-30B, can effectively emulate expert writing to generate well-written, accurate, and persuasive messages, thereby demonstrating the capability of LLMs in augmenting clinical practices of smoking cessation interventions.

Hybrid atrial fibrillation ablation.

In this state-of-the art review on hybrid atrial fibrillation (AF) ablation, we briefly focus on the pathophysiology of AF, the rationale for the hybrid approach, its technical aspects and the efficacy and safety outcomes after hybrid AF ablation, both from meta-analyses and randomized control trial data. Also, we performed a systematic search to provide a provisional overview of real-world hybrid AF ablation efficacy and safety outcomes. Furthermore, we give an insight into the 'Maastricht approach', an approach that allows us to tailor the ablation procedure to the individual patient. Finally, we reflect on future perspectives with the objective to continue improving our thoracoscopic hybrid AF ablation approach. Based on the review of the available literature, we believe it is fair to state that thoracoscopic hybrid AF ablation is a valid alternative to catheter ablation for the treatment of patients with more persistent forms of AF.

Development of the INpaTiEnt Rehabilitation App Compliance QuesTionnaire [INTERACT].

BACKGROUND: The elements of previously designed questionnaires do not take into consideration the burdens encountered in an inpatient hospital setting. The purpose of this study is to validate elements of a non-compliance survey in an in-hospital setting and discuss aspects of compliance with telerehabilitative physiotherapy in the early postoperative period. METHODS: A literature search was conducted to identify elements that prevent patients from performing their prescribed physical therapy exercises. These items were then evaluated by the expert review technique as described by Ikart. Afterwards, the synthesized survey was handed out to patients for the assessment of the quality of its items. RESULTS: The results of the expert review technique identified some conceptual and grammatical problems. This led to the adjustment of some of the elements. The quality of the resulting questionnaire was deemed to be good, as patients were able to fully understand the concepts and answer accordingly. A statistical analysis was conducted to evaluate the responses. CONCLUSIONS: The items of this second questionnaire have proven to be reliable to assess the compliance of patients in an in-hospital setting. These items will be added to the cross-culturally adapted items of a previous questionnaire.

Assessing the utility of common arguments used in expert review of in silico predictions as part of ICH M7 assessments.

Expert review of two predictions, made by complementary (quantitative) structure-activity relationship models, to an overall conclusion is a key component of using in silico tools to assess the mutagenic potential of impurities as part of the ICH M7 guideline. In lieu of a specified protocol, numerous publications have presented best practise guides, often indicating the occurrence of common prediction scenarios and the evidence required to resolve them. A semi-automated expert review tool has been implemented in Lhasa Limited's Nexus platform following collation of these common arguments and assignment to the associated prediction scenarios made by Derek Nexus and Sarah Nexus. Using datasets primarily donated by pharmaceutical companies, an automated analysis of the frequency these prediction scenarios occur, and the likelihood of the associated arguments assigning the correct resolution, could then be conducted. This article highlights that a relatively small number of common arguments may be used to accurately resolve many prediction scenarios to a single conclusion. The use of a standardised method of argumentation and assessment of evidence for a given impurity is proposed to improve the efficiency and consistency of expert review as part of an ICH M7 submission.

Misdiagnosis analysis of 2291 cases of haematolymphoid neoplasms.

Objective: To retrospectively analyze the reasons for misdiagnosis of haematolymphoid neoplasms and provide experience for improving the diagnostic level in China. Methods: A retrospective analysis was performed on 2291 cases of haematolymphoid diseases evaluated by the Department of Pathology of our hospital from 1 July 2019 to 30 June 2021. All 2291 cases were reviewed by two hematopathologist experts and classified according to the 2017 revised WHO classification criteria, supplemented immunohistochemistry (IHC), molecular biology and genetic information as needed. The diagnostic discordance between primary and expert review was evaluated. The possible causes of the diagnostic discrepancies were analyzed for each step involved in the procedure of diagnosis. Results: In total, 912 cases did not conform to the expert diagnoses among all the 2291 cases, with a total misdiagnosis rate of 39.8%. Among them, misdiagnosis between benign and malignant lesions accounted for 24.3% (222/912), misdiagnosis between haematolymphoid neoplasms and non-haematolymphoid neoplasms accounted for 3.3% (30/912), misdiagnosis among lineages accounted for 9.3% (85/912), misclassification in lymphoma subtypes accounted for 60.8% (554/912), and other misdiagnoses among benign lesions accounted for 2.3% (21/912) of cases, among which misclassification of lymphoma subtypes was the most common. Conclusion: The accurate diagnosis of haematolymphoid neoplasms is challenging, involving various types of misdiagnosis and complicated causes, however, it is important for precise treatment. Through this analysis, we aimed to highlight the importance of accurate diagnosis, avoid diagnostic pitfalls and to improve the diagnostic level in our country.

A Cancer Education Framework for Australian Medical Schools: an Announcement of a New Educational Program.

This framework draws upon national and international cancer curricula to identify the essential cancer-related learning outcomes for Australian medical students. The framework incorporates feedback from medical, radiation and surgical oncologists, haematologists, and palliative care physicians on what medical graduates need to know about cancer. The consensus view was that medical students require a basic understanding of the principles of cancer management and the opportunity to see cancer patients in a cancer service unit. The framework assumes that certain knowledge, skills, and attitudes are already embedded in current Australian medical school curricula, presenting instead only the core cancer content in order to provide a clear and concise framework designed to maximise integration within existing curricula.

Ciclosporin A Cationic Emulsion 0.1% for the Management of Dry Eye Disease: Facts That Matter for Eye-Care Providers.

Dry eye disease (DED) is a chronic inflammatory disease of the ocular surface requiring long-term therapy. Severe forms of DED generally do not respond to tear substitutes alone or combined, and often require treatment with topical anti-inflammatory agents to break the vicious circle of inflammation. This review summarises data from randomised controlled trials and real-world evidence on the efficacy and safety of ciclosporin A 0.1% cationic emulsion (Ikervis®) for the management of DED. Improvements in clinical signs and symptoms were reported from as early as 4 weeks after treatment initiation, although it can take a few months to reach the full benefits. Treatment periods of up to 12 months provide sustained benefit to patients. In the most responsive patients, treatment discontinuation is possible with no further substantial relapse over 12 months in over 65% of patients. Transient local ocular effects are the most commonly reported adverse events.

Assessing the Usability of a Clinical Decision Support System: Heuristic Evaluation.

BACKGROUND: Poor usability is a primary cause of unintended consequences related to the use of electronic health record (EHR) systems, which negatively impacts patient safety. Due to the cost and time needed to carry out iterative evaluations, many EHR components, such as clinical decision support systems (CDSSs), have not undergone rigorous usability testing prior to their deployment in clinical practice. Usability testing in the predeployment phase is crucial to eliminating usability issues and preventing costly fixes that will be needed if these issues are found after the system's implementation. OBJECTIVE: This study presents an example application of a systematic evaluation method that uses clinician experts with human-computer interaction (HCI) expertise to evaluate the usability of an electronic clinical decision support (CDS) intervention prior to its deployment in a randomized controlled trial. METHODS: We invited 6 HCI experts to participate in a heuristic evaluation of our CDS intervention. Each expert was asked to independently explore the intervention at least twice. After completing the assigned tasks using patient scenarios, each expert completed a heuristic evaluation checklist developed by Bright et al based on Nielsen's 10 heuristics. The experts also rated the overall severity of each identified heuristic violation on a scale of 0 to 4, where 0 indicates no problems and 4 indicates a usability catastrophe. Data from the experts' coded comments were synthesized, and the severity of each identified usability heuristic was analyzed. RESULTS: The 6 HCI experts included professionals from the fields of nursing (n=4), pharmaceutical science (n=1), and systems engineering (n=1). The mean overall severity scores of the identified heuristic violations ranged from 0.66 (flexibility and efficiency of use) to 2.00 (user control and freedom and error prevention), in which scores closer to 0 indicate a more usable system. The heuristic principle user control and freedom was identified as the most in need of refinement and, particularly by nonnursing HCI experts, considered as having major usability problems. In response to the heuristic match between system and the real world, the experts pointed to the reversed direction of our system's pain scale scores (1=severe pain) compared to those commonly used in clinical practice (typically 1=mild pain); although this was identified as a minor usability problem, its refinement was repeatedly emphasized by nursing HCI experts. CONCLUSIONS: Our heuristic evaluation process is simple and systematic and can be used at multiple stages of system development to reduce the time and cost needed to establish the usability of a system before its widespread implementation. Furthermore, heuristic evaluations can help organizations develop transparent reporting protocols for usability, as required by Title IV of the 21st Century Cures Act. Testing of EHRs and CDSSs by clinicians with HCI expertise in heuristic evaluation processes has the potential to reduce the frequency of testing while increasing its quality, which may reduce clinicians' cognitive workload and errors and enhance the adoption of EHRs and CDSSs.

A local QSAR model based on the stability of nitrenium ions to support the ICH M7 expert review on the mutagenicity of primary aromatic amines.

BACKGROUND: Aromatic amines, often used as intermediates for pharmaceutical synthesis, may be mutagenic and therefore pose a challenge as metabolites or impurities in drug development. However, predicting the mutagenicity of aromatic amines using commercially available, quantitative structure-activity relationship (QSAR) tools is difficult and often requires expert review. In this study, we developed a shareable QSAR tool based on nitrenium ion stability. RESULTS: The evaluation using in-house aromatic amine intermediates revealed that our model has prediction accuracy of aromatic amine mutagenicity comparable to that of commercial QSAR tools. The effect of changing the number and position of substituents on the mutagenicity of aromatic amines was successfully explained by the change in the nitrenium ion stability. Furthermore, case studies showed that our QSAR tool can support the expert review with quantitative indicators. CONCLUSIONS: This local QSAR tool will be useful as a quantitative support tool to explain the substituent effects on the mutagenicity of primary aromatic amines. By further refinement through method sharing and standardization, our tool can support the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) M7 expert review with quantitative indicators.

Identifying and validating game design elements in serious game guideline for climate change.

Climate change can simply be defined as an increase in temperature, normally referred to as global warming. Recent studies have confirmed the failure of many climate communication efforts due to the one-directional transmission of information that has transformed the audience into passive consumers of information. The young generation tends to be avid gamers, thus serious games could be a suitable medium to increase climate change awareness in order to cultivate a better attitude towards nature among this group. However, very few games focus on carbon cycle fundamentals that are directly related to climate change. Existing climate change games have been unable to improve the quality of knowledge on environmental issues due to the lack of contextualization of the carbon cycle. Thus, the purpose of this study was to develop and verify a guideline of game design elements to assist game developers in developing a climate change game that can facilitate experiential learning on climate change based on the carbon cycle. The guideline consists of 13 game elements derived from previous studies. Seven experts from both game and environmental areas were selected to review the designed guideline. The experts were given two to six weeks to evaluate the guideline and were asked to rate and comment on each game element. At the end of the review, the experts' feedback and comments were analysed and scrutinised. The results showed positive feedback from all experts. The guideline was updated based on the experts' comments, and finally a total of 12 game elements for a climate change game remained. This guideline can be applied to develop a new climate change game. This paper discusses the validation of the guideline proposed for a climate change game design.

MultiCASE Platform for In Silico Toxicology.

Predictive and computational toxicology, a highly scientific and research-based field, is rapidly progressing with wider acceptance by regulatory agencies around the world. Almost every aspect of the field has seen fundamental changes during the last decade due to the availability of more data, usage, and acceptance of a variety of predictive tools and an increase in the overall awareness. Also, the influence from the recent explosive developments in the field of artificial intelligence has been significant. However, the need for sophisticated, easy to use and well-maintained software platforms for in silico toxicological assessments remains very high. The MultiCASE suite of software is one such platform that consists of an integrated collection of software programs, tools, and databases. While providing easy-to-use and highly useful tools that are relevant at present, it has always remained at the forefront of research and development by inventing new technologies and discovering new insights in the area of QSAR, artificial intelligence, and machine learning. This chapter gives the background, an overview of the software and databases involved, and a brief description of the usage methodology with the aid of examples.

Management of symptomatic postoperative epidural hematoma in spine surgery: Medicolegal implications.

INTRODUCTION: Spine surgery is one of the specialties with the highest medicolegal risk, with a legal action initiated every 17 months per practitioner. One of the most dreaded complications is an epidural hematoma with postoperative deficit. The treatment of this complication is still being debated. We therefore conducted a retrospective study of the database of a medical liability insurer to assess perioperative factors determining the liability of the surgeon or paramedical team during an expert review in the event of a postoperative symptomatic epidural hematoma. HYPOTHESIS: To identify the factors determining the liability of the medical team in the event of a postoperative symptomatic epidural hematoma. MATERIALS AND METHODS: We retrospectively analyzed the largest French register of medicolegal expert reviews between 2011 and 2018. We identified 68 cases by entering the following keywords in this database: "spine surgery," "complications," and "epidural hematoma." After a thorough review of each case, only 14 were deemed to be truly relevant to our study. We collected for each patient the perioperative data, complications (including neurologic deficits) and their clinical course. RESULTS: Only one surgeon was accused and found liable for failing to perform a surgical revision within a reasonable timeframe (time to revision of 11 days). In 2 cases, the liability of a nurse working in the surgical department was called into question for failing to contact the surgeon upon the onset of symptoms. In the other cases (11 patients, 79%), the occurrence of a symptomatic epidural hematoma was considered a no-fault medical accident that was not caused by the surgeon. The presence of a drain did not have any medicolegal impact in the cases reviewed. CONCLUSION: The key element in medicolegal decisions is the reaction time of the healthcare teams, in particular the time between the onset of symptoms and surgical revision. According to these expert reviews, the placement of a drain was not taken into consideration during the medicolegal assessment of a postoperative symptomatic epidural hematoma. LEVEL OF EVIDENCE: II; retrospective prognostic study, investigation of patient characteristics and their impact on functional outcome.

Assessing the impact of expert knowledge on ICH M7 (Q)SAR predictions. Is expert review still needed?

The ICH M7 (R1) guideline recommends the use of complementary (Q)SAR models to assess the mutagenic potential of drug impurities as a state-of-the-art, high-throughput alternative to empirical testing. Additionally, it includes a provision for the application of expert knowledge to increase prediction confidence and resolve conflicting calls. Expert knowledge, which considers structural analogs and mechanisms of activity, has been valuable when models return an indeterminate (equivocal) result or no prediction (out-of-domain). A retrospective analysis of 1002 impurities evaluated in drug regulatory applications between April 2017 and March 2019 assessed the impact of expert review on (Q)SAR predictions. Expert knowledge overturned the default predictions for 26% of the impurities and resolved 91% of equivocal predictions and 75% of out-of-domain calls. Of the 261 overturned default predictions, 15% were upgraded to equivocal or positive and 79% were downgraded to equivocal or negative. Chemical classes with the most overturns were primary aromatic amines (46%), aldehydes (45%), Michael-reactive acceptors (37%), and non-primary alkyl halides (33%). Additionally, low confidence predictions were the most often overturned. Collectively, the results suggest that expert knowledge continues to play an important role in an ICH M7 (Q)SAR prediction workflow and triaging predictions based on chemical class and probability can improve (Q)SAR review efficiency.

Strengthening prehospital clinical practice guideline development in South Africa: Reflections from guideline experts.

INTRODUCTION: De novo (new) guideline development methods are well described and supported by numerous examples, including comprehensive checklists. However, alternative guideline development methods, which draw from existing up to date, high quality clinical practice guidelines instead of re-inventing the wheel, have not been adopted so readily, despite the potential efficiencies of such methods compared to de novo development. In Africa, guideline quality and rigour of development, especially for prehospital care, remains poor. This paper firstly describes the opinions of international guideline experts on the African Federation for Emergency Medicine guideline project, and secondly updates a framework for South African prehospital guideline development. METHODS: We conducted a qualitative study of expert reviews of an evidence-based guideline development project led by the African Federation for Emergency Medicine in 2016 for prehospital care in South Africa. We purposefully sampled key international and regional guideline experts from a range of organisations. Comments and voice memos, following a terms of reference guide, were thematically analysed through manual coding. RESULTS: A total of seven experts gave feedback. Key themes revolved around existing international clinical practice guidelines not being enough to cover context specific evidence, blurring of guideline responsibilities and output, and transparency of guideline decisions and conflicts of interest. We showcase three fit-for-purpose guideline development approaches and provide an updated alternative guideline development roadmap for low-resource settings. CONCLUSION: In order to create clinical practice guidelines that clinicians trust and use on a daily basis to change lives, guideline developers need rigorous yet pragmatic approaches that are responsive to end-user needs. Reflecting on the African Federation for Emergency Medicine prehospital guideline development project in 2016, this paper presents key guiding themes to strengthen guideline development in low- and middle-income countries and other low-resource settings and provides an updated hybrid guideline development approach.

Acute respiratory distress syndrome (ARDS) caused by the novel coronavirus disease (COVID-19): a practical comprehensive literature review.

INTRODUCTION: The exponential growth of SARS-CoV-2 virus transmission during the first months of 2020 has placed substantial pressure on most health systems around the world. The complications derived from the novel coronavirus disease (COVID-19) vary due to comorbidities, sex and age, with more than 50% of the patients requiring some level of intensive care developing acute respiratory distress syndrome (ARDS). The authors carried out an extensive and comprehensive literature review on SARS-CoV-2 infection, the clinical, pathological, and radiological presentation as well as the current treatment strategies. AREAS COVERED: Various complications caused by SARS-CoV-2 infection have been identified, the most lethal being the acute respiratory distress syndrome, caused most likely by the presence of severe immune cell response and the concomitant alveolus inflammation. The new treatment strategies are updated, and the analysis of the physiopathology is included in this review. EXPERT OPINION: ARDS is one of the most frequent complications in patients with COVID-19. Information regarding the etiology and physiopathology are still unfolding and for the prevention and amelioration, good clinical management, adequate ventilatory support and the use of systemic corticoids seem to be the most efficient way to reduce mortality and to reduce hospital lengths.